BUFFALO, NY — Two top faculty leaders at Roswell Park Cancer Institute (RPCI) have received a five-year, $2,187,881 National Cancer Institute (NCI) grant to study the antitumor effects of vitamin D on bladder cancer. Co-Principal Investigators Candace Johnson, PhD, Deputy Director of RPCI, and President and CEO Donald L. Trump, MD, FACP, will investigate the therapeutic benefits of administering high doses of the most active form of vitamin D with standard chemotherapy.
The evidence for an association between vitamin D and cancer has been growing. Vitamin D — an important component for health and a key factor in bone building, mineral metabolism and proper functioning of the immune system — is made in the body through the action of sunlight on the skin. It has been known for some time that many adults — up to 70 percent in the northeastern U.S. — have blood vitamin D levels that are substantially below normal. In addition, African-Americans, whose skin pigments block the effect of sunlight in manufacturing vitamin D, have higher mortality from certain cancers.
“It was discovered some years ago that tumor cells had receptors for vitamin D on them,” explained Dr. Johnson, who is also Chair of the Department of Pharmacology and Therapeutics and Robert Lew and Anne Wallace Chair for Translational Research. “And when vitamin D hits these receptors and binds to them, the cancer cells die or stop growing. This grant allows us to investigate the mechanism by which this occurs and how we can use vitamin D in conjunction with conventional chemotherapy to improve response to chemotherapy.”
One part of this bladder cancer investigation will explore how vitamin D induces a certain marker called p73, a protein involved in cell death. “We found that if vitamin D increases the expression of p73, then bladder cancer cells could be more sensitive to chemotherapy,” said Dr. Johnson.
“We’ve shown in many laboratory studies that high-dose vitamin D enhances the effect of chemotherapy in inhibiting and killing cancer cells. We have also shown that very high doses of the most potent form of vitamin D can be given safely with many kinds of chemotherapy,” added Dr. Trump. “Now we will explore this idea in bladder cancer, combining vitamin D and the chemotherapy drugs used to treat that disease.”
The RPCI team plans a phase I study to determine the safety of combining oral calcitriol (vitamin D) with the conventional chemotherapy agents cisplatin and gemcitabine, drugs used to treat bladder cancer. A phase II study will follow to examine the benefits of giving vitamin D plus chemotherapy prior to removal of the bladder in patients with bladder cancer that has penetrated the muscle. For patients like these, effective therapies are limited, and because bladder cancer tumors typically grow on the inside of the bladder, cancer cells are more easily accessible to monitor in the urine for molecular changes without invasive biopsies. The standard treatment for such patients involves chemotherapy with cisplatin/gemcitabine to shrink the tumors prior to surgery, followed by surgery to remove the bladder. In the trial, patients will take calcitriol plus cisplatin/gemcitaibine chemotherapy for three cycles before undergoing bladder removal.
“We will define how vitamin D causes cancer cells to die or stop growing, and use what we learn to exploit its anticancer effect therapeutically,” says Dr. Johnson. “We hope our work will lay the groundwork for more clinical trials with vitamin D and other tumor types.”
The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. RPCI, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit RPCI’s website at http://www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email firstname.lastname@example.org.
Annie Deck-Miller, Senior Media Relations Manager